4-Acetamidobenzenesulfonyl azide

A. Dimethyl diazomalonate. Into a 500-mL, round-bottomed flask is placed a large magnetic stirring bar (Note 1), 4-acetamidobenzenesulfonyl azide (72.3 mmol, 17.36 g, Note 2), acetonitrile (250 mL, Note 3), and triethylamine (76.5 mmol, 7.74 g, Note 4). The reaction mixture is cooled to 0°C, and dimethyl malonate (72.0 mmol, 9.51 g, Note 4) is slowly added over 3 - 5 min by a syringe. The reaction mixture is kept at 0 C for 10 min then stirred at room temperature for 17 hr. A thick white... 

Acetamidobenzenesulfonyl azide is obtained from Aldrich Chemical Company, Inc., and used without further purification. In addition, 4-acetamido-benzenesulfonyl azide can be synthesized from the precursor, 4-acetamidobenzene-sulfonyl chloride.2... 

The product from Step 5 (1.3 kg in 8.8 kg solution of CH2CI2) was added to 4-acetamidobenzenesulfonyl azide (1.25 kg) dissolved in 7L CH2CI2 and the solution heated to 18-21 °C with steam. Over a period of 40 minutes 2.17L EtjN was added, stirred 9 hours at 18-23 °C while monitoring the reaction by HPLC. When the reaction was completed, it was filtered, the cake was washed 3 times with 2L CH2CI2, and the slurry washed once with IL CH2CI2. The washes and filtrate were combined and extracted with 7.4L 2M cool HCl. The organic extract was dried with Na2S04 and the product isolated in >95% yield. H-NMR data supplied. 

Rhodium(ll)-catalyzed decomposition of vinyldiazomethanes in dichloromethane in the presence of dirhodium(II) tetraacetate has found wide application in the construction of seven-membered rings828,829,854. Several methods for the synthesis of the required vinyldiazomethanes are available, for example, diazo transfer from 4-acetamidobenzenesulfonyl azide in the presence of a base (triethylamine for 17, or l,8-diazabicyclo[5.4.0]undec-7-ene for less acidic precursors, e.g., 21, p 3580) to a C-H acidic compound824, 829 8=5"859 e.g., the formation of 19824. 

Should further examinations confirm their advantages over the existing reagents, it will be possible to also safely produce them on a technical scale just like p-toluenesulfonyl azide " and 4-acetamidobenzenesulfonyl azide. " ... 

DEPAA= diethyl phosphonoacetic acid T3P= propyl phosphonic anhydride DIPEA= A/,A/-diisopropylethylamine p-ABSA= 4-acetamidobenzenesulfonyl azide LHMDS= lithium bis(trimethylsilyl)amide... 

The diazo transfer reaction with sulfonyl azides has been extensively used for the preparation of diazo compounds with two electron-withdrawing groups (equation 1 ).28 Toluenesulfonyl azide (13a)29 is the standard reagent used, but due to problems of safety and ease of product separation, several alternative reagents have been developed recently. n-DodecylbenzenesuIfonyl azide (13b)30 is very effective for the preparation of crystalline diazo compounds, while p-acetamidobenzenesulfonyl azide (13c)31 or naph-thalenesulfonyl azide (13d)30 are particularly useful with fairly nonpolar compounds. Other useful reagents are methanesulfonyl azide (13e)32 and p-carboxybenzenesulfonyl azide (13f).33... 

The report stresses the advantages of p-acetamidobenzenesulfonyl azide, N3S02C6H4NHC0CH3-p,6 for preparation of diazo compounds by diazo-transfer. It is safe, inexpensive, and the sulfonamide by-product is removed by simple trituration with H20. 

Commercially available p-acetamidobenzenesulfonyl azide (Aldrich Chemical Company, Inc.) was preferred over p-dodecylbenzenesulfonyl azide (Danheiser, R. L Miller, R. F. Brisbois, Org. Synth. 1995, 73, 134, Note 9 Ref. 4a), or methanesulfonyl azide4 for reasons of safety, yield, and ease of manipulation. 

The carbocyclic [6-7] core of guanacastepenes was prepared by. D. Trauner et al. using the intramolecular reaction between carbenoids derived from diazo carbonyl compounds and furans. The required diazo carbonyl substrate was synthesized using p-acetamidobenzenesulfonyl azide (p-ABSA) as the diazo-donor component in the Regitz diazo transfer reaction. 

The azido/n.v(dicthykirnino)phosphoniurn bromide appears to be an exceptionaly safe diazo reagent stable to shock, friction, heating, and even flame.It reacts smoothly with diethyl 1-(ethoxycarbonyl)methylphosphonate in Et2O at room temperature in the presence of t-BuOK or another alkoxide to give diethyl 1-ethoxycarbonyl-l-diazomethylphosphonate in 70% yield (Scheme 8.32). 5 5 ° Mild diazo transfer has recently been achieved in excellent yields (85%) through the use of para-acetamidobenzenesulfonyl azide at O C ... 

B. Ethyl diazoacetoacetate. A 2-L, round-bottomed flask equipped with a magnetic stirrer is charged with 26.0 g (0.20 mol) of ethyl acetoacetate, 49.0 g, (0.20 mol) of p-acetamidobenzenesulfonyl azide and 1.5 L of acetonitrile. The reaction vessel Is cooled in an ice bath, and 60.6 g (0.60 mol) of triethylamine is added to the stirring mixture In one portion. The reaction mixture is warmed to room temperature and stirred for 12 hr. The solvent Is removed under reduced pressure, and the residue Is triturated with 500 mL of a 1 1 mixture of ether/petroleum ether. The mixture is filtered to remove the sulfonamide by-product, and the filtrate and wash are concentrated under reduced pressure. The crude product is purified by chromatograpy on silica gel (130 g. Note 5) with ether/petroleum ether (1 4) as eluant to yield 28.5 g (91%) of ethyl diazoacetoacetate as a yellow oil (Note 6). 

Caution These reactions, which involve toxic reagents, should be carried out in an effident hood. Although p-acetamidobenzenesulfonyl azide exhibited no impact sensitivity, proper caution should be exercised with all azide compounds. 

A. p-Acetamidobenzenesulfonyl azide. A 2-L Erlenmeyer flask equipped with a magnetic stirrer is charged with 117.0 g (0.50 mol) of p-acetamidobenzenesulfonyl... 

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